UV activated peroxymonosulfate synergistically removes Microcystis aeruginosa and Chlorella vulgaris
Journal of environmental chemical engineering,
Год журнала:
2025,
Номер
13(2), С. 115379 - 115379
Опубликована: Янв. 8, 2025
Язык: Английский
The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer
Journal of Bioenergetics and Biomembranes,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 8, 2025
Abstract
Otto
Warburg
originally
proposed
that
cancer
arose
from
a
two-step
process.
The
first
step
involved
chronic
insufficiency
of
mitochondrial
oxidative
phosphorylation
(OxPhos),
while
the
second
protracted
compensatory
energy
synthesis
through
lactic
acid
fermentation.
His
extensive
findings
showed
oxygen
consumption
was
lower
lactate
production
higher
in
cancerous
tissues
than
non-cancerous
tissues.
considered
both
and
extracellular
as
accurate
markers
for
ATP
OxPhos
glycolysis,
respectively.
Warburg’s
hypothesis
challenged
showing
remained
high
some
cells
despite
elevated
suggesting
largely
unimpaired.
New
information
indicates
neither
nor
are
surrogates
quantification
cells.
also
did
not
know
significant
amount
could
come
glutamine-driven
substrate
level
glutaminolysis
pathway
with
succinate
produced
end
product,
thus
confounding
linkage
to
origin
within
mitochondria.
Moreover,
new
shows
cytoplasmic
lipid
droplets
aerobic
fermentation
biomarkers
insufficiency.
original
can
now
be
linked
more
complete
understanding
how
underlies
dysregulated
cell
growth.
These
address
several
questionable
assumptions
regarding
allowing
field
advance
effective
therapeutic
strategies
less
toxic
metabolic
management
prevention
cancer.
Язык: Английский
Phenotypic screening reveals a highly selective phthalimide-based compound with antileishmanial activity
PLoS neglected tropical diseases,
Год журнала:
2024,
Номер
18(3), С. e0012050 - e0012050
Опубликована: Март 25, 2024
Pharmacophores
such
as
hydroxyethylamine
(HEA)
and
phthalimide
(PHT)
have
been
identified
potential
synthons
for
the
development
of
compounds
against
various
parasitic
infections.
In
order
to
further
advance
our
progress,
we
conducted
an
experiment
utilising
a
collection
PHT
HEA
derivatives
through
phenotypic
screening
diverse
set
protist
parasites.
This
approach
led
identification
number
that
exhibited
significant
effects
on
survival
Entamoeba
histolytica
,
Trypanosoma
brucei
multiple
life-cycle
stages
Leishmania
spp
.
The
hits
were
pursued
due
pressing
necessity
expand
repertoire
reliable,
cost-effective,
efficient
medications
treatment
leishmaniases.
Antileishmanials
must
possess
essential
capability
efficiently
penetrate
host
cells
their
compartments
in
disease
context,
effectively
eliminate
intracellular
parasite.
Hence,
performed
study
assess
effectiveness
eradicating
L
infantum
amastigotes
model
macrophage
infection.
Among
eleven
growth
inhibitors
with
low-micromolar
potency,
PHT-39,
which
carries
trifluoromethyl
substitution,
demonstrated
highest
efficacy
intramacrophage
assay,
EC50
1.2
+/-
3.2
μM.
Cytotoxicity
testing
PHT-39
HepG2
indicated
promising
selectivity
over
90-fold.
A
chemogenomic
profiling
was
using
orthology-based
method
elucidate
mode
action
PHT-39.
genome-wide
RNA
interference
library
T
sensitivity
determinants
included
P-type
ATPase
is
crucial
uptake
miltefosine
amphotericin,
strongly
indicating
shared
route
cellular
entry.
Notwithstanding
favourable
properties
Plasmodium
berghei
infection
model,
unable
eradicate
major
murine
cutaneous
leishmaniasis.
Currently,
undergoing
derivatization
optimize
its
pharmacological
characteristics.
Язык: Английский
Amino Acid and Glucose Fermentation Maintain ATP Content in Mouse and Human Malignant Glioma Cells
Derek C. Lee,
Linh Ta,
Purna Mukherjee
и другие.
ASN NEURO,
Год журнала:
2024,
Номер
16(1)
Опубликована: Янв. 1, 2024
Energy
is
necessary
for
tumor
cell
viability
and
growth.
Aerobic
glucose-driven
lactic
acid
fermentation
a
common
metabolic
phenotype
seen
in
most
cancers
including
malignant
gliomas.
This
linked
to
abnormalities
mitochondrial
structure
function.
A
luciferin-luciferase
bioluminescence
ATP
assay
was
used
measure
the
influence
of
amino
acids,
glucose,
oxygen
on
content
mouse
(VM-M3
CT-2A)
human
(U-87MG)
glioma
cells
that
differed
biology,
genetic
background,
species
origin.
Oxygen
consumption
measured
using
Resipher
system.
Extracellular
lactate
succinate
were
as
end
products
glycolysis
glutaminolysis
pathways,
respectively.
The
results
showed
that:
(1)
glutamine
source
irrespective
oxygen.
No
other
could
replace
sustaining
viability;
(2)
persisted
absence
glucose
under
hypoxia,
ruling
out
substantial
contribution
through
either
or
oxidative
phosphorylation
(OxPhos)
these
conditions;
(3)
Mitochondrial
complex
IV
inhibition
not
an
accurate
production
OxPhos.
glutaminase
inhibitor,
6-diazo-5-oxo-L-norleucine
(DON),
reduced
export
grown
glutamine.
data
suggests
substrate
level
glutamine-driven
pathway
contributes
cells.
new
model
presented
highlighting
synergistic
interaction
between
high-throughput
pathways
drive
growth
maintain
aerobic
both
Язык: Английский
TrAGEDy: Trajectory Alignment of Gene Expression Dynamics
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Дек. 22, 2022
1
Abstract
Motivation
Single-cell
transcriptomics
sequencing
is
used
to
compare
different
biological
processes.
However,
often,
those
processes
are
asymmetric
which
difficult
integrate.
Current
approaches
often
rely
on
integrating
samples
from
each
condition
before
either
cluster-based
comparisons
or
analysis
of
an
inferred
shared
trajectory.
Results
We
present
Trajectory
Alignment
Gene
Expression
Dynamics
(TrAGEDy),
allows
the
alignment
independent
trajectories
avoid
need
for
error-prone
integration
steps.
Across
simulated
datasets,
TrAGEDy
returns
correct
underlying
outperforming
current
tools
fail
capture
complexity
alignments.
When
applied
real
captures
more
biologically
relevant
genes
and
processes,
other
differential
expression
methods
detect
when
looking
at
developments
T
cells
bloodstream
forms
Trypanosoma
brucei
affected
by
genetic
knockouts.
Availability
Implementation
freely
available
https://github.com/No2Ross/TrAGEDy
,
implemented
in
R.
Contact
[email protected]
Язык: Английский
Amino Acid and Glucose Fermentation Maintain ATP Content in Mouse and Human Malignant Glioma Cells
Derek C. Lee,
Linh Ta,
Purna Mukherjee
и другие.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 22, 2024
Abstract
Energy
is
necessary
for
tumor
cell
viability
and
growth.
Aerobic
glucose-driven
lactic
acid
fermentation
a
common
metabolic
phenotype
seen
in
most
cancers
including
malignant
gliomas.
This
linked
to
abnormalities
mitochondrial
structure
function.
A
luciferin-luciferase
bioluminescence
ATP
assay
was
used
measure
the
influence
of
amino
acids,
glucose,
oxygen
on
content
mouse
(VM-M3
CT-2A)
human
(U-87MG)
glioma
cells
that
differed
biology,
genetic
background,
species
origin.
Oxygen
consumption
measured
using
Resipher
system.
Extracellular
lactate
succinate
were
as
end
products
glycolysis
glutaminolysis
pathways,
respectively.
The
results
showed
that:
1)
glutamine
source
irrespective
oxygen.
No
other
could
replace
sustaining
viability;
2)
persisted
absence
glucose
under
hypoxia,
ruling
out
substantial
contribution
through
either
or
oxidative
phosphorylation
(OxPhos)
these
conditions;
3)
Mitochondrial
complex
IV
inhibition
not
an
accurate
production
OxPhos.
glutaminase
inhibitor,
6-diazo-5-oxo-L-norleucine
(DON),
reduced
export
grown
glutamine.
data
suggests
substrate
level
glutamine-driven
pathway
contributes
cells.
new
model
presented
highlighting
synergistic
interaction
between
high-throughput
pathways
drive
growth
maintain
aerobic
both
Summary
statement
Malignant
gliomas,
regardless
origin
species,
rely
mechanisms
due
OxPhos
insufficiency.
Glucose
together
are
sufficient
dysregulated
growth,
whereas
neither
nor
sufficient.
Язык: Английский
Venturicidin A affects the mitochondrial membrane potential and induces kDNA loss in Trypanosoma brucei
Antimicrobial Agents and Chemotherapy,
Год журнала:
2024,
Номер
68(7)
Опубликована: Июнь 13, 2024
ABSTRACT
Neglected
tropical
diseases
caused
by
trypanosomatid
parasites
have
devastating
health
and
economic
consequences,
especially
in
areas.
New
drugs
or
new
combination
therapies
to
fight
these
are
urgently
needed.
Venturicidin
A,
a
macrolide
extracted
from
Streptomyces
,
inhibits
the
ATP
synthase
complex
of
fungi
bacteria.
However,
its
effect
on
trypanosomatids
is
not
fully
understood.
In
this
study,
we
tested
venturicidin
A
panel
using
Alamar
Blue
assays
found
it
be
highly
active
against
Trypanosoma
brucei
Leishmania
donovani
but
much
less
so
evansi
.
Using
fluorescence
microscopy,
observed
rapid
loss
mitochondrial
membrane
potential
T.
bloodstream
forms
upon
treatment.
Additionally,
report
DNA
approximately
40%–50%
treated
parasites.
We
conclude
that
targets
suggest
could
candidate
for
anti-trypanosomatid
drug
repurposing,
combinations,
medicinal
chemistry
programs.
Язык: Английский
Inhibition of L-Threonine Dehydrogenase from Trypanosoma cruzi reduces glycine and acetate production and interferes with parasite growth and viability.
Journal of Biological Chemistry,
Год журнала:
2024,
Номер
unknown, С. 108080 - 108080
Опубликована: Дек. 1, 2024
Язык: Английский
Venturicidin A affects the mitochondrial membrane potential and induces kDNA loss inTrypanosoma brucei
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 15, 2024
Abstract
Neglected
tropical
diseases
caused
by
trypanosomatid
parasites
have
devastating
health
and
economic
consequences,
especially
in
areas.
New
drugs
or
new
combination
therapies
to
fight
these
are
urgently
needed.
Venturicidin
A,
a
macrolide
extracted
from
Streptomyces
,
inhibits
the
ATP
synthase
complex
of
fungi
bacteria.
However,
its
effect
on
trypanosomatids
is
not
fully
understood.
In
this
study,
we
tested
venturicidin
A
panel
using
Alamar
Blue
assays
found
it
be
highly
active
against
Trypanosoma
brucei
Leishmania
donovani
but
much
less
so
evansi
.
Using
fluorescence
microscopy
observed
rapid
loss
mitochondrial
membrane
potential
T.
bloodstream
forms
upon
treatment.
Additionally,
report
DNA
approximately
40
50%
treated
parasites.
We
conclude
that
targets
suggest
could
candidate
for
antitrypanosomatid
drug
repurposing,
combinations,
medicinal
chemistry
programs.
Язык: Английский